Improvement of Psoriasis During Sunitinib Therapy for Renal Cell Carcinoma

Sunitinib is an oral tyrosine kinase inhibitor, which is indicated for the treatment of renal cell carcinoma and gastrointestinal stromal tumors. The authors report the case of a patient who underwent treatment for renal cell carcinoma and noted additional benefit by improvement in his psoriatic skin lesions. This may be attributed to the antiangiogenic activity of sunitinib by inhibition of vascular endothelial growth factor receptors.     

Recovery of 131I from alkaline solution of n-irradiated tellurium target using a tiny Dowex-1 column

A simple and inexpensive ion-exchange chromatography method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO₂) target was developed and tested using ¹³¹I. The radiochemical separation was performed using a very small Dowex-1×8 ion-exchange column. The overall radiochemical yield for the complete separation of ¹³¹I was 92±1.8 (standard deviation) % (n=8). The separated nca ¹³¹I was of high, ～99%, radionuclidic and radiochemical purity and did not contain detectable amounts of the target material. This method may be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.     

Human heme oxygenase-1 deficiency presenting with hemolysis, nephritis, and asplenia

Heme oxygenase-1 (HO-1) is a stress-induced enzyme that catalyses the oxidation of heme to biliverdin. The primary deficiency of this enzyme has been shown in HO-1 knockout mice, and is characterized by intrauterine death and chronic inflammation. The first case of human HO-1 deficiency was reported in 1999. Human HO-1 deficiency has been observed to involve the endothelial cells more severely, resulting in hemolysis and disseminated intravascular coagulation. We report another case of human HO-1 deficiency in a young girl with congenital asplenia, who presented with severe hemolysis, inflammation, nephritis, which was refractory to therapy with corticosteroids, cyclophosphamide, and rituximab.     

First case of Tropicoporus tropicalis keratitis in an immunocompetent host from India and review of the literature

Tropicoporus tropicalis is an environmental basidiomycete that has been implicated in nine cases of cutaneous (n = 7) and pulmonary (n = 2) human infections predominantly in chronic granulomatous disease patients. We report here the first case of keratitis caused by Tropicoporus tropicalis in a 40-year-old immunocompetent patient, who presented with sudden diminution of vision in right eye. Corneal scrapings revealed hyaline, septate hyphae in microscopy and culture showed growth of white non-sporulating mycelial growth which was confirmed as Tropicoporus tropicalis by sequencing of ITS region of 28S rDNA. The patient was initiated on topical voriconazole along with natamycin, gatifloxacin and atropine drops. However, despite treatment, corneal ulcer perforated, for which penetrating keratoplasty was performed. Thereafter, he was prescribed amphotericin B (AMB) drops sixteen times a day and ketoconazole 200 mg twice a day with no recurrence reported over one year of follow up. The case represents the first case of infection by this fungus from India and also is the first case to be reported in an immunocompetent host.     

Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy

Very small embryonic-like stem cells (VSELs) are possibly lost during cord blood banking and bone marrow (BM) processing for autologus stem cell therapy mainly because of their small size. The present study was conducted on human umbilical cord blood (UCB, n=6) and discarded red blood cells (RBC) fraction obtained after separation of mononuclear cells from human BM (n=6), to test this hypothesis. The results show that VSELs, which are pluripotent stem cells with maximum regenerative potential, settle along with the RBCs during Ficoll-Hypaque density separation. These cells are very small in size (3-5 μm), have high nucleo-cytoplasmic ratio, and express nuclear Oct-4, cell surface protein SSEA-4, and other pluripotent markers such as Nanog, Sox-2, Rex-1, and Tert as indicated by immunolocalization and quantitative polymerase chain reaction (Q-PCR) studies. Interestingly, a distinct population of slightly larger, round hematopoietic stem cells (HSCs) with cytoplasmic Oct-4 were detected in the "buffy" coat, which usually gets banked or used during autologus stem cell therapy. Immunohistochemical studies on the umbilical cord tissue (UCT) sections (n=3) showed the presence of nuclear Oct-4-positive VSELs and many fibroblast-like mesenchymal stem cells (MSCs) with cytoplasmic Oct-4. These VSELs with nuclear Oct-4, detected in UCB, UCT, and discarded RBC fraction obtained after BM processing, may persist throughout life, maintain tissue homeostasis, and undergo asymmetric cell division to self-renew as well as produce larger progenitor stem cells, viz. HSCs or MSCs, which follow differentiation trajectories depending on the somatic niche. Hence, it can be concluded that the true stem cells in adult body tissues are the VSELs, whereas the HSCs and MSCs are actually progenitor stem cells that arise by asymmetric cell division of VSELs. The results of the present study may help explain low efficacy reported during adult autologous stem cell trials, wherein unknowingly progenitor stem cells are injected rather than the pluripotent stem cells with maximum regenerative potential.     

ICOS ligand expression is essential for allergic airway hyperresponsiveness

Inducible co-stimulator ligand (ICOSL) is a rather newly defined co-stimulatory molecule, which, through interaction with ICOS expressed on T cells, plays an important role in T-cell activation, differentiation and function. T(h)2-type immune responses are critical for the development and maintenance of allergic responses including asthma. Using knockout (KO) mice, we have assessed the role of ICOSL in allergic airway inflammation and responsiveness using a standard mouse asthma model induced by ovalbumin (OVA) sensitization and challenge. Our data show that OVA-treated ICOSL KO mice exhibit significantly less lung eosinophilic infiltration, histopathology, mucus production and virtually no airway hyperresponsiveness in contrast to wild-type (Wt) counterparts. Serum antibody analysis showed that antigen-specific IgG1, IgG2a and IgE titers in ICOSL KO mice were significantly lower than those of Wt controls. Also, CD4(+) T cells isolated from ICOSL KO mice produced less T(h)2 cytokines (IL-4, IL-5, IL-10 and IL-13) but more T(h)1 (IFN-γ) and IL-17 than their Wt controls. Taken together, we conclude that ICOSL plays an important role in predisposing individuals to allergic airway hyperresponsiveness by enhancing IgE antibody class switching and T(h)2 cytokine production and diminishing the T(h)17 response and airway eosinophilia.     

Sleep disturbances in Phelan-McDermid syndrome: Clinical and metabolic profiling of 56 individuals

Phelan-McDermid Syndrome (PMS) is caused by deletions at chromosome 22q13.3 or pathogenic/likely pathogenic SHANK3 variants. The clinical presentation is extremely variable and includes global developmental delay/intellectual disability (ID), seizures, neonatal hypotonia, and sleep disturbances, among others. This study investigated the prevalence of sleep disturbances, and the genetic and metabolic features associated with them, in a cohort of 56 individuals with PMS. Sleep data were collected via standardized observer/caregiver questionnaires, while genetic data from array-CGH and sequencing of 9 candidate genes within the 22q13.3 region, and metabolic profiling utilized the Biolog Phenotype Mammalian MicroArray plates. Sleep disturbances were present in 64.3% of individuals with PMS, with the most common problem being waking during the night (39%). Sleep disturbances were more prevalent in individuals with a SHANK3 pathogenic variant (89%) compared to subjects with 22q13.3 deletions of any size (59.6%). Distinct metabolic profiles for individuals with PMS with and without sleep disturbances were also identified. These data are helpful information for recognizing and managing sleep disturbances in individuals with PMS, outlining the main candidate gene for this neurological manifestation, and highlighting potential biomarkers for early identification of at-risk subjects and molecular targets for novel treatment approaches.     

Fibrotomy with diode laser (980 nm) and habit correlation in oral submucous fibrosis: a report of 30 cases

To evaluate the efficacy of laser fibrotomy in patients with oral submucous fibrosis (OSMF) and also to correlate the habit variables causing OSMF. Thirty patients diagnosed clinically and histopathologically with OSMF were included in the study. Laser fibrotomy was done under local anesthesia using Zolar diode laser (980 nm frequency) at 2-W power in contact mode with fibro-optic cutting tip. The patients were advised to practice mouth-opening exercises rigorously, and topical corticosteroid was given for burning sensation and pain for 6 months. Pre- and post-treatment comparison of mouth opening, burning sensation, tongue protrusion, and cheek flexibility was analyzed after a follow-up period of 9 months. After a follow-up period of 9 months from the surgical intervention, the mean value of difference in pre- and post-treatment of VAS score, mouth opening, and tongue protrusion was found to be 3.3?±?2.1, 7.7?±?5.1, 1.6?±?2.7, and 0.38?±?0.61 respectively. Using the Wilcoxon signed rank test, all the above difference in mean was found to be significant with p value <?0.05. With above suggested significant results, lasers can provide an alternative and better means for surgical fibrotomy, relieving trismus in moderate OSMF as they are minimally invasive, cause less hemorrhage, and have faster healing and minimal surgical site scaring and relapse.     

Reasons for extraction in a group of Libyan patients

Aims and objectives: To investigate the pattern and causes of tooth loss in patients among eastern part of Libya. Materials and methods: This study carried out at Faculty of Dentistry, Garyounis University, Benghazi, Libya. The out patients undergoing extractions at the Oral Surgery Department were randomly selected for this study between Jan 2007 and March 2008 where a total of 9,570 extractions were performed on 8,514 patients. The incidence and reasons for tooth extraction, their distribution according to age and sex were studied. Results: Males had more teeth extracted than females. Forty patients had one or more systemic illnesses, 34 were on regular medication. The study revealed two major causes of tooth loss: dental caries (55.90%) and periodontal diseases (34.42%). Other important causes were trauma (3.76%), impaction (1.83%), prosthodontic reasons (2.19%), and orthodontic reasons (1.30%) and others which included extraction where the tooth was associated with a tumour, cyst or supernumerary tooth (1.61%). Dental caries was the main causes of tooth loss during the 2nd, 3rd and 4th decades. While periodontal diseases were the prevalent aetiological factor during the 4th, 5th, 6th and 7th decades of life. The posterior teeth most frequently extracted due to dental caries were lower first molars (43.92%). Whereas anterior teeth were more frequently extracted due to periodontal diseases (28%) with the remaining posterior teeth also being extracted (7%).